N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response.

Abstract

Viral myocarditis caused by Coxsackievirus B (CVB) infection is a severe inflammatory disease of the myocardium, which may develop to cardiomyopathy and heart failure. No effective specific treatment is available. Our previous study demonstrated that suppression of proinflammatory caspase-1 activation effectively inhibited CVB replication. N-acetyl cysteine (NAC) is a widely used antioxidant. In this study, we found that NAC significantly alleviated the myocardial injury caused by CVB type 3 (CVB3) under in vivo condition. Importantly, NAC treatment simultaneously suppressed viral replication and inflammatory response in both myocardium and cell culture. The antiviral and anti-inflammation mechanism of NAC, while independent of its antioxidant property, relies on its inhibition on caspase-1 activation. Moreover, NAC promotes procaspase-1 degradation via ubiquitin proteasome system, which further contributes to caspase-1 down-regulation. NAC also inhibits the activity of viral proteases. Taken together, this study shows that NAC exerts potent anti-CVB and anti-inflammation effect through targeting caspase-1. Given that NAC is a clinically approved medicine, we recommend NAC as a valuable therapeutic agent for viral myocarditis caused by CVB.

• Authors: Yao Wang, Shuoxuan Zhao, Yang Chen, Ying Wang, Tianying Wang, Xiaoman Wo, Yanyan Dong, Jian Zhang, Weizhen Xu, Cong Qu, Xiaofeng Feng, Xiaoyu Wu, Yan Wang, Zhaohua Zhong, Wenran Zhao
• Journal: Antiviral research (Antiviral Res) Vol. 179 Pg. 104699 (07 2020) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 31883926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Caspase Inhibitors
• Proteasome Endopeptidase Complex
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Animals
• Animals, Newborn
• Antiviral Agents (therapeutic use)
• Caspase Inhibitors (therapeutic use)
• Coxsackievirus Infections (complications, drug therapy)
• Enterovirus B, Human (drug effects, physiology)
• HeLa Cells
• Humans
• Inflammation (drug therapy, virology)
• Mice, Inbred BALB C
• Myocarditis (drug therapy, virology)
• Proteasome Endopeptidase Complex (metabolism)
• Specific Pathogen-Free Organisms
• Virus Replication (drug effects)